Ontak

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Infusion Reactions

Infusion reactions, defined as symptoms occurring within 24 hours of infusion
and resolving within 48 hours of the last infusion in that course, were reported
in 70.5% (165/234) of Ontak (denileukin diftitox) -treated patients across 3 clinical studies utilizing
the approved doses and schedule. Serious infusion reactions were reported in
8.1% (19/234) of Ontak (denileukin diftitox) -treated patients. There have been post-marketing reports
of infusion reactions resulting in death. For patients completing at least 4
courses of Ontak treatment in Study 1[see Clinical
Studies], the incidence of infusion reactions was lower in the 3rd
and 4th cycles as compared to the 1st and 2nd
cycles of Ontak (denileukin diftitox) .

Capillary Leak Syndrome

Capillary leak syndrome was defined as the occurrence of at least 2 of the
following 3 symptoms (hypotension, edema, serum albumin < 3.0 g/dL) at any
time during Ontak (denileukin diftitox) therapy. These symptoms were not required to occur simultaneously
to be characterized as capillary leak syndrome. As defined, capillary leak syndrome
was reported in 32.5% (76/234) of Ontak (denileukin diftitox) -treated patients. Among these 76 patients
with capillary leak syndrome, one-third required hospitalization or medical
intervention to prevent hospitalization. There have been post-marketing reports
of capillary leak syndrome resulting in death.

The onset of symptoms in patients with capillary leak syndrome may be delayed,
occurring up to 2 weeks following infusion. Symptoms may persist or worsen after
the cessation of Ontak (denileukin diftitox) .

Regularly assess patients for weight gain, new onset or worsening edema, hypotension
(including orthostatic changes) and monitor serum albumin levels prior to the
initiation of each course of therapy and more often as clinically indicated.
Withhold Ontak (denileukin diftitox) for serum albumin levels of less than 3.0 g/dL [see WARNINGS
AND PRECAUTIONS].

Visual Loss

Loss of visual acuity, usually with loss of color vision, with or without retinal pigment mottling has been reported following administration of Ontak (denileukin diftitox) . Recovery
was reported in some of the affected patients; however, most patients reported
persistent visual impairment.

CD25 Tumor Expression and Evaluation

Confirm that the patient's malignant cells express CD25 prior to administration
of Ontak (denileukin diftitox) . A testing service for the assay of CD25 expression in tumor biopsy
samples is available. For information on this service call 877-873-4724.

Laboratory Monitoring/Hypoalbuminemia

Monitor serum albumin levels prior to the initiation of each treatment course.
Withhold administration of Ontak (denileukin diftitox) if serum albumin levels are less than 3.0 g/dL
[see DOSAGE AND ADMINISTRATION and WARNINGS
AND PRECAUTIONS].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

There have been no studies to assess the carcinogenic potential of denileukin
diftitox. Denileukin diftitox showed no evidence of mutagenicity in the Ames
test and the chromosomal aberration assay. There have been no studies to assess
the effect of denileukin diftitox on fertility.

Use In Specific Populations

Pregnancy

It is not known whether Ontak (denileukin diftitox) can cause fetal harm when administered to a pregnant
woman or can affect reproductive capacity. Animal reproduction studies have
not been conducted with Ontak (denileukin diftitox) . Ontak (denileukin diftitox) should be given to a pregnant woman only
if clearly needed.

Nursing Mothers

It is not known whether Ontak (denileukin diftitox) is excreted in human milk. Because many drugs
are excreted in human milk, and because of the potential for serious adverse
reactions in nursing infants from Ontak (denileukin diftitox) , a decision should be made whether to
discontinue nursing or to discontinue Ontak (denileukin diftitox) , taking into account the importance
of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Ontak (denileukin diftitox) did not include sufficient numbers of subjects aged
65 and older to determine whether they respond differently from younger subjects.

Last reviewed on RxList: 12/4/2008
This monograph has been modified to include the generic and brand name in many instances.